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Background: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated., Methods: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions., Results: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions)., Conclusion: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions., (© 2024. The Author(s).)

Objective: Pilocytic astrocytoma (PA) is rare in adults comprising 5.1% of the primary central nervous system tumors. The aim is to describe the first Brazilian series of adult patients with PA and compare its features with the available literature., Methods: We retrospectively review all patients 18 years or older with PA from our institution's database from 1991 to 2018. We analyzed information regarding clinical presentation, location, imaging features, extent of resection, adjuvant treatments, and follow-up., Results: Twenty-three patients with PA were analyzed: 60.9% male; median age 26 years. The most frequent symptoms were headache (34.8%) and seizure (26.1%). Temporal and parietal lobes were the most common locations, 21.7% each. All patients underwent a surgical procedure, gross total resection in 40.9%, subtotal resection in 22.7%, and biopsy in 27.3%. Adjuvant treatment with radiotherapy was performed in 2 patients. Only 4 patients had disease progression, 2 after gross total resection and 2 after subtotal resection. They were all alive and without evidence of new progression at the last follow-up (October 2018). Median overall survival was not reached after a median follow-up time of 88.9 months., Conclusions: This is the first Brazilian series regarding adults with PA, and our patients had a favorable outcome as reported in recent literature reviews. The tumor's prevalence reduces within older patients and supratentorial lesions are more frequent, especially on the temporal lobe. There was no significant relationship between location and progression, although according to the literature the extent of resection remains the most important prognostic factor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia-reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location. The aim of this study was to evaluate, for the first time, the anti-tumor activity of Amblyomin-X in 4 primary cultures derived from pediatric anaplastic posterior fossa EPN, Group A (anaplastic, WHO grade III) and one primary culture of a high grade neuroepithelial tumor with MN1 alteration, which was initially misdiagnosed as EPN: i) by in vitro assays: comparisons of temozolomide and cisplatin; ii) by intracranial xenograft model. Amblyomin-X was able to induce cell death in EPN cells in a more significant percentage compared to cisplatin. The cytotoxic effects of Amblyomin-X were not detected on hFSCs used as control, as opposed to cisplatin-treatment, which promoted a substantial effect in the hAFSCs viability. TEM analysis showed ultrastructural alterations related to the process of cell death: mitochondrial degeneration, autophagosomes and aggregate-like structures. MRI and histopathological analyzes demonstrated significant tumor mass regression. Our results suggest that Amblyomin-X has a selective effect on tumor cells by inducing apoptotic cell death and may be a therapeutic option for Group AEPNs.

Background: Previous studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133 + GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism. However, the role in the modulation of this tropism of the subpopulation of CD133 + cells, which initiate GBM and the mechanisms underlying the tropism of MSCs to CD133 + GBM cells and their effects on tumor development, remains poorly defined., Methods/results: We found that isolated and cultured MSCs (human umbilical cord blood MSCs) express CCR2 and CXCR4, the respective receptors for MCP-1/CCL2 and SDF-1/CXCL12, and demonstrated, in vitro, that MCP-1/CCL2 and SDF-1/CXC12, secreted by CD133 + GBM cells from primary cell cultures, induce the migration of MSCs. In addition, we confirmed that after in vivo GBM tumor establishment, by stereotaxic implantation of the CD133 + GBM cells labeled with Qdots (705 nm), MSCs labeled with multimodal iron oxide nanoparticles (MION) conjugated to rhodamine-B (Rh-B) (MION-Rh), infused by caudal vein, were able to cross the blood-brain barrier of the animal and migrate to the tumor region. Evaluation GBM tumors histology showed that groups that received MSC demonstrated tumor development, glial invasiveness, and detection of a high number of cycling cells., Conclusions: Therefore, in this study, we validated the chemotactic effect of MCP-1/CCL2 and SDF-1/CXCL12 in mediating the migration of MSCs toward CD133 + GBM cells. However, we observed that, after infiltrating the tumor, MSCs promote tumor growth in vivo probably by release of exosomes. Thus, the use of these cells as a therapeutic carrier strategy to target GBM cells must be approached with caution.

Background: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs., Results: We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth., Conclusions: We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs., Methods: In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients ( n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

The purpose of this study was to evaluate spontaneous necrosis as a possible isolated factor for progression and recurrence in grade I meningiomas classified according to the current World Health Organization (WHO) classification. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The 2016 WHO classification of central nervous system tumors stratifies meningiomas in grades I (benign), II (atypical), and III (malignant), according to histopathological aspects and the risk of progression or recurrence. Among 110 patients with intracranial meningiomas, 70 were WHO grade I meningiomas with no findings of atypia (G1WON), 15 were WHO grade I with necrosis (G1WN), 21 were WHO grade II (G2), and 4 were WHO grade III (G3). The mean follow-up was 5.9 ± 0.2 years. High performance scale (KPS ≥ 80) was different (p < 0.001) between WHO grade I meningiomas without (81.4%) and with (60%) necrosis. The 5-year mortality rate was 1.4, 6.7 and 5.9% for G1WON, G1WN and G2, respectively, with significant difference (p = 0.011) related to the presence of necrosis. The risk of recurrence was 3.7 times higher in G1WN than in G1WON (p = 0.017), and 4.2 times in G2 (p = 0.010). Progression-free survival (PFS) was clearly higher in patients with G1WON compared to G1WN and G2 (p = 0.002 and p < 0.001, respectively). There was no significant difference in PFS between G1WN and G2 (p = 0.692). Retreatment was also superior in meningioma with necrosis. Our findings provide clear statistical data to consider that patients with benign meningiomas and histologic findings of spontaneous necrosis are at increased risk of progression and recurrence compared to those with benign lesion without atypical features. Statistical analysis curves also suggest that these lesions behave more similarly to those currently classified as WHO grade II meningioma.

Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types., Competing Interests: The authors indicate no potential conflicts of interest.

Background Although germ cell tumors and pineal cell tumors account for most of the histologic tumor subtypes, > 17 different tumors can arise in this location. We report a rare case of a low-grade oligodendroglioma that arose in the pineal region. Clinical Presentation A young woman complaining of a headache underwent magnetic resonance imaging that showed a mass in the pineal region and mild hydrocephalus. A ventriculoperitoneal shunt was performed followed by a near-total tumor removal, due to tumor invasion of the tectal plate and thalamus. The histologic examination confirmed the diagnosis of a low-grade oligodendroglioma. The patient then underwent chemotherapy and radiotherapy as adjuvant therapies. Conclusion Although the pineal region is a common place for a large number of tumoral lesions, low-grade oligodendrogliomas are extremely rare in this location. This case is only the second account of a benign oligodendroglioma of the pineal region reported in the literature.

Background: Fusiform aneurysms of cerebellar arteries are rare. Different surgical techniques to address these challenging lesions have been described, and their application depends on whether the goal is to maintain the flow in the parent vessel or to occlude it., Case Description: The authors reported a case of a fusiform aneurysm located in the lateral pontomesencephalic segment of the superior cerebellar artery (SCA) in a 32-year-old man who presented with subarachnoid hemorrhage. The patient was subjected to aneurysm trapping followed by a bypass between the superficial temporal artery (STA) and SCA and had an uneventful recovery., Conclusions: Although only a few cases of fusiform aneurysms in the supracerebellar artery have been reported in the literature, the treatment strategies adopted were diverse. In selected cases of patients in good neurological condition with ruptured fusiform aneurysms at the proximal segments of SCA and who have poor evidence of collateral supply, the possibility of a STA-SCA bypass with aneurysm trapping must be considered. A review of the current treatment modalities of this pathology is also presented.

In this paper, the authors present the case of a patient with multifocal intradural extramedullary ependymoma, and they review 18 previously reported cases. A 32-year-old man presented to the authors' institution with a 1-month history of partial medullary syndrome. Magnetic resonance imaging of the neuraxis revealed multifocal intradural extramedullary lesions at the bulbomedullary junction and C2-3, T5-11, L-2, L-4, L-5, and sacrum. Histological examination revealed a WHO Grade II ependymoma. The literature survey yielded 18 cases of ependymoma at the same location; none of them were multifocal at presentation. The authors analyzed the epidemiological, clinical, and surgical features of all 19 cases reported to date, including the present case. Patients' ages ranged from 24 to 69 years; 15 patients were women and 4 were men. The time elapsed from symptom onset to diagnosis ranged from 1 month to 8 years. Pain (in 13 patients) and medullary syndrome (in 12) were reported as the initial symptoms (information was not provided for 1 patient). Tumors were predominantly located in the thoracic spine (11), but they also occurred in the cervicothoracic (3), cervical (2), and lumbar (2) spine. The remaining tumor was multifocal. Solitary extramedullary tumors were found intraoperatively in 13 patients; 3 were described as exophytic and 3 as extramedullary with some degree of medullary invasion. Histological examination revealed 9 WHO Grade II tumors, 4 Grade III tumors, and 1 myxopapillary tumor. Data obtained for the remaining cases proved inconclusive. The clinical condition improved in 11 patients, remained stable in 2, and worsened (recurrence or progression) in 6. Of the 4 patients with Grade II tumors who presented with recurrence or neuraxis spreading, 3 had meningeal infiltration or adhesion to the pia mater, which does not rule out the possibility of neoplastic remnants in that area. Intradural extramedullary ependymomas are rare, they predominate in women in the 5th decade of life, and pain is the most frequent initial symptom. The extent of resection and the presence of meningeal infiltration seem to be key determinants of prognosis. The present case is the first intradural extramedullary ependymoma (with the exception of those occurring at the conus medullaris and terminal filum) with multiple lesions at presentation.

Objective: Giant pituitary adenomas (> or =40 mm) pose a major management challenge. We describe the experience of a single surgeon and a dedicated neuro-endocrine team with multimodality treatment of these tumours in three specialized institutions., Design: Retrospective data set analyses., Patients: Fifty-one consecutive patients with a giant adenoma (39 endocrine-inactive, 12 endocrine-active; mean tumour diameter 45 mm) treated over 10 years by an endonasal transsphenoidal approach were included. All patients had surgical resection followed by radiotherapy and/or medical therapy as judged necessary., Measurements: Hormonal and visual status, extent of resection, tumour control rates, complications and use of medical and radiotherapy were evaluated., Results: Surgery resulted in gross total, near total and subtotal removal in21 (41%), 10 (20%) and 20 (39%) patients respectively. Complete tumour removal was associated with absence of cavernous sinus invasion (P < 0.001). Long-term endocrine function improved in 49% of patients and new endocrinopathy occurred in 14.6%; 76% required long-term hormone replacement therapy. Vision improved in 81.5% of the patients and there was no visual worsening. At the last follow up (median 30 months), tumour control was achieved in 96% of patients: 59% with surgery alone, 20% with surgery plus focussed radiotherapy, 18% with surgery and medical therapy and two with all three modalities., Conclusions: Endonasal surgery provides effective initial treatment for patients with giant adenomas. Multimodality therapy was needed in almost 50% of patients and this rate will likely increase with longer follow up. Close collaboration of neurosurgeons with endocrinologists and radiation oncologists is essential for optimal treatment of patients with these challenging tumours.

Objective: Endonasal and supraorbital "eyebrow" craniotomies are increasingly being used to remove craniopharyngiomas and tuberculum sellae meningiomas. Herein, we assess the relative advantages, disadvantages, and selection criteria of these 2 keyhole approaches., Methods: All consecutive patients who had endonasal or supraorbital removal of a craniopharyngioma or tuberculum sellae meningioma were analyzed., Results: Of 43 patients, 22 had a craniopharyngioma (18 endonasal, 4 supraorbital), and 21 had a meningioma (12 endonasal, 7 supraorbital, 2 both routes); 33% had prior surgery. Craniopharyngiomas were primarily retrochiasmal in location in 78% of endonasal cases versus 25% of supraorbital cases (P = 0.08). Meningiomas were larger when approached by the supraorbital route versus the endonasal route (33 +/- 10 versus 25 +/- 8 mm, respectively; P = 0.008). Endoscopy was used in 84% of endonasal approaches and in 31% of supraorbital approaches (P = 0.001). Of patients having first-time surgery for a craniopharyngioma (n = 14) or meningioma (n = 15), total/near total removal was achieved in 83% and 80% of patients by the endonasal route and in 50% and 80% of patients by the supraorbital route, respectively. Vision improved in 87% and 70% of patients who had surgery by an endonasal versus supraorbital route, respectively (P = 0.3). Visual deterioration occurred in 2 patients with meningiomas, 1 by endonasal (7%), and 1 by supraorbital (11%) removal. The endonasal approach was associated with a higher rate of postoperative cerebrospinal fluid leaks (16 versus 0%; P = 0.3), 4 of 5 of which occurred in patients with meningioma., Conclusion: The endonasal route is preferred for removal of most retrochiasmal craniopharyngiomas, whereas the supraorbital route is recommended for meningiomas larger than 30 to 35 mm or with growth beyond the supraclinoid carotid arteries. For smaller midline tumors, either approach can be used, depending on surgeon experience and tumor anatomy. Compared with traditional craniotomies, the major limitation of both approaches is a narrow surgical corridor. The endonasal approach has the added challenges of restricted lateral suprasellar access, a greater need for endoscopy, and a more demanding cranial base repair.

THE DIRECT ENDONASAL transsphenoidal approach to the sella with the operating microscope was initially described more than 20 years ago. Herein, we describe the technique, its evolution, and lessons learned over a 10-year period for treating pituitary adenomas and other parasellar pathology. From July 1998 to January 2008, 812 patients underwent a total of 881 operations for a pituitary adenoma (n = 605), Rathke's cleft cyst (n = 59), craniopharyngioma (n = 26), parasellar meningioma (n = 23), chordoma (n = 18), or other pathological condition (n = 81). Of these, 118 operations (13%) included an extended approach to the suprasellar, infrasellar/clival, or cavernous sinus regions. Endoscopic assistance was used in 163 cases (19%) overall, including 36% of the last 200 cases in the series and 18 (72%) of the last 25 extended endonasal cases. Surgical complications included 19 postoperative cerebrospinal fluid leaks (2%), 6 postoperative hematomas (0.7%), 4 carotid artery injuries (0.4%), 4 new permanent neurological deficits (0.4%), 3 cases of bacterial meningitis (0.3%), and 2 deaths (0.2%). The overall complication rate was higher in the first 500 cases in the series and in extended approach cases. Major technical modifications over the 10-year period included increased use of shorter (60-70 mm) endonasal speculums for greater instrument maneuverability and visualization, the micro-Doppler probe for cavernous carotid artery localization, endoscopy for more panoramic visualization, and a graded cerebrospinal fluid leak repair protocol. These changes appear to have collectively and incrementally made the approach safer and more effective. In summary, the endonasal approach provides a minimally invasive route for removal of pituitary adenomas and other parasellar tumors.

Unlabelled: Fibromatosis is a locally aggressive, proliferative fibroblastic lesion affecting musculoaponeurotic structures, most often in the limbs and trunk. Intracranial fibromatosis is extremely rare and requires aggressive treatment to prevent recurrence., Case Description: We present the case of a 20 year old woman with aggressive skull base fibromatosis. The lesion extended through the sphenoid, ethmoid sinus and nasal cavity, destroying the right roof of the orbit and penetrating in anterior skull base. A combined anterior craniofacial approach was performed; complete resection with surgical margin was impossible due to the localization of the tumor and relation to important neurovascular structures. Complete resection with surgical margin is often impossible because of its widely infiltrative nature. Radiotherapy and chemotherapy are often required to improve local control of the lesion.

Background: Intrathoracic meningocele is a rare pathology, almost always associated with neurofibromatosis type I and with a few cases related in the literature. In the majority of cases cysts are small or asymptomatic, and the surgery is indicated when big or symptomatic cysts are present. We report a case of giant intrathoracic cysts surgically extirpated through out thoracotomy., Case: A 59-year-old male with familiar Von Recklinghausen's disease which developed thoracic radicular pain after a fall. On examination he presented some difficulty in walking fast and dyspneia on small efforts. The chest plain x-ray showed the presence of 3 huge left side intrathoracic cysts (10 to 15cm). The patient was submitted to a surgical treatment and complete extirpation of the cysts was performed through a left side thoracotomy. During the surgery a fourth smaller cyst was detected and also extirpated. Evolution was uneventful and the patient remains well in these last 12 years. This finding of intrathoracic cysts related to neurofibromatosis type I is rare and is probably unique in the literature the presence of 4 huge cysts in one side of the thorax.